title: Dimeric HER2-specific affibody molecules inhibit proliferation of the SKBR-3 breast cancer cell line.
abstract: HER2-specific affibody molecules in different formats have previously been shown to be useful tumor targeting agents for radionuclide-based imaging and therapy applications, but their biological effect on tumor cells is not well known. In this study, two dimeric ((Z(HER2:4))(2) and (Z(HER2:342))(2)) and one monomeric (Z(HER2:342)) HER2-specific affibody molecules are investigated with respect to biological activity. Both (Z(HER2:4))(2) and (Z(HER2:342))(2) were found to decrease the growth rate of SKBR-3 cells to the same extent as the antibody trastuzumab. When the substances were removed, the cells treated with the dimeric affibody molecules continued to be growth suppressed while the cells treated with trastuzumab immediately resumed normal proliferation. The effects of Z(HER2:342) were minor on both proliferation and cell signaling. The dimeric (Z(HER2:4))(2) and (Z(HER2:342))(2) both reduced growth of SKBR-3 cells and may prove therapeutically useful either by themselves or as carriers of radionuclides or other cytotoxic agents.
authors.affiliation: Department of Oncology, Radiology and Clinical Immunology, Division of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden. Electronic address: Lina.Ekerljung@bms.uu.se.
authors.forename: Lina
authors.initials: L
authors.lastname: Ekerljung
authors.affiliation: Affibody AB, P.O. Box 20137, SE-161 02 Bromma, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Lindborg
authors.affiliation: Department of Oncology, Radiology and Clinical Immunology, Division of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Gedda
authors.affiliation: Affibody AB, P.O. Box 20137, SE-161 02 Bromma, Sweden.
authors.forename: Fredrik Y
authors.initials: FY
authors.lastname: Frejd
authors.affiliation: Department of Oncology, Radiology and Clinical Immunology, Division of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
authors.forename: Jörgen
authors.initials: J
authors.lastname: Carlsson
authors.affiliation: Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Lennartsson
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D015374:Biosensing Techniques; D001943:Breast Neoplasms / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019281:Dimerization; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000494:pharmacology*; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D048049:Extracellular Signal-Regulated MAP Kinases; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D000068878:Trastuzumab; C515865:Z(HER2.4)2 affibody; C533351:affibody (ZHER2-342)2